The square was designed and constructed in the early 19th century, shortly after King Otto moved the capital of the newly born Greek Kingdom from Nafplio to Athens in 1834. It was designed as one of the two central squares of modern Athens, situated to what were then the eastern boundaries of the city. The second square was Omonoia Square, to the north of the city. Even though King Otto's Royal Palace was at first planned to be erected on Omonia Square, a location overlooking the eastern square was deemed a better option. Thus, the square's first name was "Palace Square". Work for the construction of the Old Palace to the north of the square, started in 1836 and lasted until 1843.[1]

 Dimitrios Kallergis on horseback demanding Constitution, Otto and Amalia at the windows of the Royal Palace.

In late July 1843,[1] a popular and military uprising took place in the Greek Capital on September 3, 1843. Soldiers under Dimitrios Kallergis gathered in front of the palace and demanded the granting of constitution. King Otto was then obliged to grant the first Constitution of Greece.[2] In memory of the event, the palace square was renamed to Constitution Square or Syntagma Square in Greek.

In the summer of 1900, in the Square, films were projected outdoors, in the cafés.[3]

Between 2010 and 2012, the square was the site of mass protests by crowds of many thousands of people, due to the worsening economic situation during the Greek government debt crisis.